The UCSD MHCRC is exploring the behavioral-psychopharmacologic-psychobiologic interface, with a major focus on the study of affect disorders. Since first awarded in October 1977, the UCSD MHCRC has become an effective research system and inpatient clinical research unit, having studied approximately 200 individual patients/volunteers who have participated in approximately 800 separate experiments. This MHCRC is pioneering work exploring the role of endogenous opioid polypeptides in affective disorders, the role of chronobiologic phenomena in the etiology of affective disorders, the possibility that magnesium may regulate affect, and the possibility that adrenergic factors may be of etiologic and therapeutic significance in the affective disorders, schizophrenia, and adult hyperkinesis. Interacting with the above psychobiologic-psychopharmacologic studies are a variety of studies of the cognitive, memory, interpersonal, neuropsychologic, psychophysiologic, psychomotor, and clinical psychologic effects of such psychotropic drugs as lithium, imipramine, haloperidol, marijuana, methylphenidate, and such psychopathologic states as mania, depression, schizophrenia, and adult hyperkinesis. Sophisticated methodologies have been developed to measure serum desipramine, imipramine, amytriptyline, haloperidol, choline, beta-endorphin, and such neurophoriones as growth hormone, prolactin, cortisol and luteinizing hormone, and a variety of catecholamine metabolites, which serve as dependent measures for the above studies. Clinical and basic scientists, working together on allied projects, using animal and human models, interact intensively in a mutually enriching scientific ambience. Over 100 publications have resulted from these efforts. Within the above framework, multiple collaborations have developed and are continuing to expand. The research plan over the next five years is to have continued scientific growth focused on understanding the nature of major psychiatric disorders and their treatment.